CU23917B1 - PROCESS FOR THE PREPARATION AND USE OF A BIVALENT VACCINE AGAINST ADDICTION TO MORPHINE-HEROINE - Google Patents

PROCESS FOR THE PREPARATION AND USE OF A BIVALENT VACCINE AGAINST ADDICTION TO MORPHINE-HEROINE

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Publication number
CU23917B1
CU23917B1 CU2007000002A CU20070002A CU23917B1 CU 23917 B1 CU23917 B1 CU 23917B1 CU 2007000002 A CU2007000002 A CU 2007000002A CU 20070002 A CU20070002 A CU 20070002A CU 23917 B1 CU23917 B1 CU 23917B1
Authority
CU
Cuba
Prior art keywords
morphine
addiction
structural
revealed
heroin
Prior art date
Application number
CU2007000002A
Other languages
Spanish (es)
Other versions
CU20070002A7 (en
Inventor
Palma Benito Antón
Gelman Philippe Leff
Original Assignee
Inst Nac De Psiquiatría Ramón De La Fuentes Muñíz
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Inst Nac De Psiquiatría Ramón De La Fuentes Muñíz filed Critical Inst Nac De Psiquiatría Ramón De La Fuentes Muñíz
Publication of CU20070002A7 publication Critical patent/CU20070002A7/en
Publication of CU23917B1 publication Critical patent/CU23917B1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267—Gram-positive bacteria
    • C07K16/1282—Clostridium (G)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/0013—Therapeutic immunisation against small organic molecules, e.g. cocaine, nicotine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/02—Bacterial antigens
    • A61K39/08—Clostridium, e.g. Clostridium tetani
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/385—Haptens or antigens, bound to carriers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6415—Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/643—Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/646—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36—Opioid-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/44—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/575—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 humoral response
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6031—Proteins
    • A61K2039/6037—Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/70—Multivalent vaccine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
    • Y10T436/141111—Diverse hetero atoms in same or different rings [e.g., alkaloids, opiates, etc.]

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Neurology (AREA)
  • Virology (AREA)
  • Biomedical Technology (AREA)
  • Toxicology (AREA)
  • Neurosurgery (AREA)
  • Addiction (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Se revela el diseño estructural, métodos de preparación y composición química de dos formulaciones estructurales de vacunas bivalentes contra la adicción a morfina-heroína (morfina-6-hemiscuccinil-EDC-TFCS-toxoide tetánico y 3-0-carboximetilmorfina-EDC-TFCS-toxoide tetánico, adecuados para su empleo en la vacunación en el humano, los cuales son capaces de inducir la síntesis de anticuerpos policlonales contra este opiáceo adictivo y contra su análogo estructural la heroína, a través de su administración repetida in vivo, en un esquema de vacunación activa en estudios de fase preclínica en el modelo animal del roedor. También se revela el paradigma de vacunación activa con estos inmunógenos, los cuales son capaces de inducir una respuesta inmunológica humoral de altos títulos de anticuerpos específicos séricos consolidada con memoria a largo plazo contra esta dos drogas. En forma complementaria, también se revela que estas composiciones químicas de inmunógenos tienen capacidades de conferir inmunoprotección eficaz contra la adicción a la morfina y su congénere estructural altamente activo, la heroína, en el modelo farmacológico de autoadministración intravenosa adictiva de estos dos opiáceos en el roedor. Finalmente, se discuten las implicaciones terapéuticas del empleo potencial ulterior de estos inmunoconjugados en esquemas de vacunación activa para el tratamiento de la adicción a estas dos drogas en el humano.The structural design, preparation methods and chemical composition of two structural formulations of bivalent vaccines against morphine-heroin addiction (morphine-6-hemiscuccinyl-EDC-TFCS-tetanus toxoid and 3-0-carboxymethylmorphine-EDC-TFCS-) are revealed Tetanus toxoid, suitable for use in vaccination in humans, which are capable of inducing the synthesis of polyclonal antibodies against this addictive opioid and against its structural analogue heroin, through repeated administration in vivo, in a scheme of Active vaccination in preclinical phase studies in the rodent animal model The active vaccination paradigm with these immunogens is also revealed, which are capable of inducing a humoral immune response of high titers of specific serum antibodies consolidated with long-term memory against these two drugs. In addition, it is also revealed that these chemical immunogen compositions s have the ability to confer effective immunoprotection against morphine addiction and its highly active structural congener, heroin, in the pharmacological model of addictive intravenous self-administration of these two opioids in the rodent. Finally, the therapeutic implications of the subsequent potential use of these immunoconjugates in active vaccination schemes for the treatment of addiction to these two drugs in humans are discussed.

CU2007000002A 2004-07-07 2007-01-05 PROCESS FOR THE PREPARATION AND USE OF A BIVALENT VACCINE AGAINST ADDICTION TO MORPHINE-HEROINE CU23917B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
MXPA04006617A MXPA04006617A (en) 2004-07-07 2004-07-07 Method of preparing and using a bivalent vaccine against morphine/heroin addiction.
PCT/MX2005/000049 WO2006004390A2 (en) 2004-07-07 2005-07-05 Preparation and use of a bivalent vaccine against morphine-heroin addiction

Publications (2)

Publication Number Publication Date
CU20070002A7 CU20070002A7 (en) 2009-09-08
CU23917B1 true CU23917B1 (en) 2013-07-31

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Country Status (15)

Country Link
US (4) US8008457B2 (en)
EP (1) EP1767221B1 (en)
AR (1) AR049962A1 (en)
BR (1) BRPI0513024A (en)
CA (1) CA2573042C (en)
CU (1) CU23917B1 (en)
CY (1) CY1114673T1 (en)
DK (1) DK1767221T3 (en)
ES (1) ES2435769T3 (en)
MX (1) MXPA04006617A (en)
PE (1) PE20060377A1 (en)
PL (1) PL1767221T3 (en)
PT (1) PT1767221E (en)
SI (1) SI1767221T1 (en)
WO (1) WO2006004390A2 (en)

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MXPA04006617A (en) 2004-07-07 2006-01-12 Inst Nac De Psiquiatria Ramon Method of preparing and using a bivalent vaccine against morphine/heroin addiction.
US8170546B2 (en) 2006-03-22 2012-05-01 Broadcom Corporation Client device characterization of other client device transmissions and reporting of signal qualities to access point(s)
EP1982729A1 (en) * 2007-04-20 2008-10-22 Cytos Biotechnology AG Vaccination Regimen for B-Cell Vaccines
EP2482838A4 (en) * 2009-09-30 2013-04-10 Toxcure Inc Use of botulinum neurotoxin to treat substance addictions
CN102002049B (en) * 2010-10-12 2013-01-02 北京大学 Antigen and preparation method and application thereof
CN102539764A (en) * 2010-12-27 2012-07-04 北京库尔科技有限公司 Pethidine hydrochloride detection kit and preparation method thereof
EP2717057A1 (en) * 2012-10-04 2014-04-09 Cisbio Bioassays Morphine-6-glucuronide derivatives, immunogens and immunoassay
RU2526807C2 (en) * 2012-11-28 2014-08-27 Общество с ограниченной ответственностью "ДИАМЕДИКА" ООО "ДИАМЕДИКА" Synthetic immunogen for protection against toxic action of narcotic and psychoactive substances
US9127008B2 (en) 2013-03-15 2015-09-08 Johnson Matthey Public Limited Company Morphine sulfate methanolic solvate, processes for making same and related compositions and methods for treating pain
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US11305010B2 (en) 2016-01-21 2022-04-19 The Scripps Research Institute Synthetic opioid vaccine
WO2019094528A1 (en) 2017-11-09 2019-05-16 The Scripps Research Institute An improved heroin vaccine
WO2020012245A1 (en) 2018-07-13 2020-01-16 Alkermes Pharma Ireland Limited Thienothiophene-naltrexone prodrugs for long-acting injectable compositions
US10799496B2 (en) 2018-07-13 2020-10-13 Alkermes Pharma Ireland Limited Naphthylenyl compounds for long-acting injectable compositions and related methods
US10975099B2 (en) 2018-11-05 2021-04-13 Alkermes Pharma Ireland Limited Thiophene compounds for long-acting injectable compositions and related methods
RU2703494C1 (en) * 2018-11-12 2019-10-18 Федеральное государственное унитарное предприятие "Государственный научно-исследовательский институт особо чистых биопрепаратов" Федерального медико-биологического агентства Monoclonal antibody 6g1 to morphine derivatives
WO2024238822A1 (en) * 2023-05-17 2024-11-21 Regents Of The University Of Minnesota Heroin vaccine compositions and methods thereof

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MXPA04006617A (en) 2004-07-07 2006-01-12 Inst Nac De Psiquiatria Ramon Method of preparing and using a bivalent vaccine against morphine/heroin addiction.

Also Published As

Publication number Publication date
US20130236478A1 (en) 2013-09-12
ES2435769T3 (en) 2013-12-23
WO2006004390A3 (en) 2006-09-21
PE20060377A1 (en) 2006-05-05
WO2006004390A2 (en) 2006-01-12
CA2573042A1 (en) 2006-01-12
AR049962A1 (en) 2006-09-20
EP1767221B1 (en) 2013-08-21
US20150064212A1 (en) 2015-03-05
CY1114673T1 (en) 2016-10-05
US8357375B2 (en) 2013-01-22
US20110318381A1 (en) 2011-12-29
CA2573042C (en) 2013-01-15
US8008457B2 (en) 2011-08-30
MXPA04006617A (en) 2006-01-12
PT1767221E (en) 2013-11-27
PL1767221T3 (en) 2014-02-28
SI1767221T1 (en) 2014-01-31
DK1767221T3 (en) 2013-11-25
CU20070002A7 (en) 2009-09-08
US20080241183A1 (en) 2008-10-02
EP1767221A2 (en) 2007-03-28
US8916170B2 (en) 2014-12-23
BRPI0513024A (en) 2008-04-22

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